Causes/pathogenesis

TB is a mainly airborne infectious disease caused by
M. tuberculosis
. Organisms are spread by droplets in the air from individuals with active TB (‘contagious patients’) who cough, sneeze, sing or speak. The highest risk of acquiring TB infection is among individuals intensively exposed at a short distance for a prolonged period of time (‘close contacts’).

Following infection, one of two clinical outcomes is possible: 1) early development of active disease (so-called ‘primary TB’), which occurs particularly in small children and immunocompromised patients); and 2) latent TB infection (LTBI), which occurs in the majority of infected individuals. The lifetime risk of developing clinical TB after infection is 5–10% in the immunocompetent. The cumulative risk of developing TB is correlated with the age at primary infection: it is estimated that children who are infected after close contact with a contagious case have a 30–50% risk of developing TB. Furthermore, several medical, social and environmental conditions impairing the immune system can increase the risk of active TB: HIV/AIDS, diabetes mellitus, chronic renal failure, silicosis, exposure to immunosuppressive drugs, tobacco smoking and malignancy. Preventive drug treatment of infected individuals at higher risk of reactivation can significantly decrease the probability of them developing active TB.

Poor clinical and public health management of individuals with latent or active disease can favour the emergence and spread of MDR-TB. This is, in essence, a man-made phenomenon caused by inadequate treatment, including human errors related to any phase of the drug-delivery process involving regimen choice (for instance, the addition of a single drug to a failing regimen, prescription of low quality-assured drugs) and duration, drug dose, treatment adherence, infection control and other determinants (such as poverty and difficult access to the healthcare system). Inadequate drug treatment may promote the selection of pre-existing resistant strains or the emergence of new resistant strains.